The present proposal will attempt to delineate the predisposing factors that cause some individuals to develop hyponatremia when given diuretics. This complication of diuretic therapy occurs primarily in the elderly patient, and thus the propensity for diuretic hyponatremia may be related to the physiologic changes associated with aging. To study for specific mechanisms, the following two hypotheses will be tested: (1) In some patients diuretics produce hyponatremia because of an underlying increase in vasopressin secretion. (2) In some patients with diuretic-induced hyponatremia there is a preexisting deficiency in renin and aldosterone secretion. Patients aged 65 or older with diuretic hyponatremia will be studied after having discontinued diuretic therapy for 2 weeks. Then water-loading studies will be carried out to assess suppressibility of vasopressin secretion. The stimulatory response of the renin-aldosterone system will be examined following diuresis. These findings will be compared with an equal number of elderly control subjects. It is anticipated that subgroups of patients with differences in vasopressin and aldosterone secretory status will be found. Multivariate analysis of clinical features will be used to identify those clinical correlates that could lead to recognition of patients at greatest risk for diuretic hyponatremia.